A spatially resolved atlas of the human lung characterizes a gland-associated immune niche.
Nat Genet
; 55(1): 66-77, 2023 01.
Article
en En
| MEDLINE
| ID: mdl-36543915
ABSTRACT
Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable at lungcellatlas.org ). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal and nerve bundle micro-environments. We identify and implicate peribronchial fibroblasts in lung disease. Importantly, we discover and validate a survival niche for IgA plasma cells in the airway submucosal glands (SMG). We show that gland epithelial cells recruit B cells and IgA plasma cells, and promote longevity and antibody secretion locally through expression of CCL28, APRIL and IL-6. This new 'gland-associated immune niche' has implications for respiratory health.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Mucosa Respiratoria
/
Pulmón
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article